Recent developments in cochlear physiology and molecular biology have paved the way for new and innovative ways of treating and preventing sensorineural hearing loss. These advances will ultimately benefit millions of individuals. However, for this to occur, it will be necessary to develop a safe and reliable mechanism for delivering bioactive compounds directly to the inner ear. The goal of this collaborative research effort is to design and develop a versatile long-term drug delivery system for the treatment of inner ear disorders. Working together, biomedical engineers from Draper Laboratory with experience and expertise in the development of drug delivery microsystems, and clinicians and scientists from the Massachusetts Eye and Ear Infirmary with expertise in inner ear physiology, pharmacology and otologic surgery will engineer, evaluate and perfect a drug delivery system for the treatment of inner ear disorders. This device will have broad application and the potential for revolutionizing the treatment of hearing loss. The design concept includes an implanted device that fits within the mastoid cavity of humans. The device contains an externally-programmable pump to recirculate perilymph, an intracochlear catheter inserted into the scala tympani through a cochleostomy, a mixing chamber with externally programmable delivery of concentrated bioactive compounds, and sensors for detecting and transmitting flow and pressure information. The core of the system is derived from a novel drug dispensing microsystem that the Draper team has designed, fabricated, and tested over the past several years. The ultra-miniaturized device is a complete, longterm (one year and greater) delivery system, containing therapeutic compound, dispensing mechanism, control electronics, and power supply. The aims of the proposal are to (1) develop an interface to the inner ear suitable for chronic, continuous recirculation of and infusion of compounds into perilymph; (2) develop an integrated, micromachined, fluid control system; (3) establish surgical procedures and determine device form factor constraints for implantation in the mastoid cavity; (4) develop an implantable drug storage reservoir, filling, and release mechanism appropriate for a range of candidate therapies; (5) develop low power control electronics, telemetry, and specify power source; and (6) evaluate safety and efficacy in preliminary animal experiments, using prototype devices to deliver compounds to the inner ear. [unreadable] [unreadable] [unreadable]